Disc Medicine (IRON) Wells Fargo 21st Annual Healthcare Conference summary

DISC-3405 program update

• DISC-3405, a monoclonal antibody targeting TMPRSS6, restricts iron to manage excess red blood cell production in polycythemia vera (PV) patients.

• The trial enrolled ahead of schedule, with promising initial data from cohort A showing effective iron restriction and mechanism engagement.

• Reduction in phlebotomy rate from about four to 0.6 per unit time, with over 60% of patients phlebotomy-free; stable dose interval shows high 70% phlebotomy-free rate.

• Side effects are minimal, with almost no anemia or injection site reactions observed, potentially distinguishing the antibody approach.

• The program aims for frontline use, potentially displacing hydroxyurea, with a well-established regulatory path and phase III planned after end of phase II.

Competitive landscape and market opportunity for PV

• Iron restriction agents in PV show similar efficacy, so differentiation focuses on safety, convenience, and side effect profile.

• PV market is sizable, with 150,000 U.S. patients and 50,000-100,000 managed by phlebotomy; iron-restricting drugs could replace phlebotomy for most.

• Commercial opportunity is significant but competitive, with pricing expected in line with other anemia treatments.

• Initial adoption likely among phlebotomy-managed patients, with potential to expand to broader PV population.

• Learnings from PV may apply to sickle cell disease, where a similar iron restriction approach is being explored.

Bitopertin and APOLLO phase III program

• Bitopertin targets a rare disease with only one approved therapy requiring surgical implant; phase III APOLLO trial designed for traditional approval after accelerated path was denied.

• APOLLO trial uses co-primary endpoints (protoporphyrin IX and time in light at month 6) to demonstrate clinical benefit, with robust phase II data informing design.

• Sample size re-estimation confirmed phase III variability matches phase II, supporting statistical powering for a 50% effect size.

• Market size estimates range from 3,000-6,000 engaged U.S. patients, with up to 14,000 identified in claims data; launch will focus on patients already in trials and centers of excellence.

• Oral agents like bitopertin are expected to replace current therapies due to convenience and robust efficacy, especially in reducing pain attacks.